Pacing guidewire

ABSTRACT

Guidewires and methods for transmitting electrical stimuli to a heart and for guiding and supporting the delivery of elongate treatment devices within the heart are disclosed. A guidewire can comprise an elongate body, including first and second elongate conductors, and at least first and second electrodes. A distal end portion of the elongate body can include a preformed bias shape, such as a pigtail-shaped region, on which the first and second electrodes can be located. The preformed bias shape can optionally be non-coplanar relative to an intermediate portion of the elongate body. The first and second elongate conductors can be formed of a single structure or two or more electrically connected structures. The conductors can extend from proximal end portions to distal end portions that electrically connect to the first and second electrodes. A corewire can extend the length of the elongate body, can at least partially form the first conductor, and can be at least partially surrounded by the second conductor.

CLAIM OF PRIORITY

This is a continuation of U.S. patent application Ser. No. 16/214,800,entitled “PACING GUIDEWIRE” and filed Dec. 10, 2018, now U.S. Pat. No.10,758,725, which is a continuation of U.S. patent application Ser. No.15/455,265, entitled “PACING GUIDEWIRE” and filed Mar. 10, 2017, nowU.S. Pat. No. 10,173,052, which claims the benefit of priority under 35U.S.C. § 119(e) to Daniels et al., U.S. Provisional Patent ApplicationSer. No. 62/310,044, entitled “PACING GUIDEWIRE” and filed on Mar. 18,2016, to Daniels et al., U.S. Provisional Patent Application Ser. No.62/346,214, entitled “PACING GUIDEWIRE” and filed on Jun. 6, 2016, toDaniels et al., U.S. Provisional Patent Application Ser. No. 62/378,258,entitled “PACING GUIDEWIRE” and filed on Aug. 23, 2016, and to Danielset al., U.S. Provisional Patent Application Ser. No. 62/436,750,entitled “PACING GUIDEWIRE” and filed on Dec. 20, 2016, each of which isherein incorporated by reference in its entirety.

TECHNICAL FIELD

This patent document relates to medical devices. More particularly, butnot by way of limitation, the patent document relates to guidewires.

BACKGROUND

Heart valve replacement may be indicated when there is a narrowing of anative heart valve or when the native valve leaks or regurgitates, suchas when the valve's leaflets are calcified.

The native valve can be excised and replaced with either a biologictissue valve or a mechanical valve. Mechanical valves require lifelonganticoagulant medication to prevent blood clot formation, and clickingof the valve can often be heard through a patient's chest. Biologictissue valves typically do not require such medication and do not click.Tissue valves can be obtained from cadavers or can be porcine or bovinebased, and the valves can be attached to cloth-covered synthetic ringsor leaflet support frames that are securable to a patient's heart valveannulus.

Conventional heart valve surgery is an open heart procedure conductedunder general anesthesia with significant concomitant risks, includingbleeding, infection, stroke, heart attack, arrhythmia, renal failure,adverse reactions to the anesthesia medications, or sudden death. Anincision is made through the patient's sternum, and the patient's heartis stopped while blood flow is rerouted through a heart-lung bypassmachine. The first two or three days following conventional heart valvesurgery are often spent in an intensive care unit where heart functionscan be closely monitored. The average hospital stay followingconventional heart valve surgery is between one and two weeks, withseveral more weeks required for complete recovery.

Advancements in minimally-invasive surgery and interventional cardiologyhave encouraged some physicians to pursue percutaneous replacement of aheart valve, including the deployment of an expandable prosthetic heartvalve device across the native diseased heart valve (which permanentlyholds the native valve open). The prosthetic heart valve device can bedesigned for percutaneous delivery in a cardiac catheterizationlaboratory under local anesthesia using fluoroscopic guidance, therebyavoiding general anesthesia and open-heart surgery.

OVERVIEW

The present inventors recognize that guidewires play an important rolein the field of percutaneous replacement of a heart valve, includingpercutaneous transcatheter aortic valve implantation (TAVI),transcatheter aortic valve replacement (TAVR), balloon valvuloplasty(BV) or transcatheter mitral valve replacement (TMVR). The presentinventors further recognize that there is a need for guidewires andrelated methods that can reduce the time for, and increase the chancesof, a successful percutaneous implantation of a prosthetic heart valvedevice.

This patent document discloses pacing guidewires that facilitate theperformance of TAVI, TAVR, BV or TMVR procedures by (i) providing goodsupport for the over-the-wire (OTW) delivery of elongate treatmentdevices with low chance of perforation or other damage of vessels, thenative aortic or mitral valve, or cardiac tissues through which theguidewire is inserted, and (ii) inducing and maintaining cardiacventricular tachycardia during certain phases of such procedures. Apacing guidewire can comprise an elongate body, including first andsecond conductors, and at least first and second electrodes. Theelongate body can extend from a proximal end portion to a distal endportion with an intermediate portion therebetween. The at least firstand second electrodes have one of a positive or negative polarity andcan be spaced between 1 centimeter (cm) and 10 cm apart, for example, invarying configurations along a preformed bias shape at the distal endportion of the elongate body. The first elongate conductor can extendfrom a proximal end portion to a distal end portion that is electricallyconnected to the first electrode. Similarly, the second elongateconductor can extend from a proximal end portion to a distal end portionthat is electrically connected to the second electrode.

A method for transmitting electrical stimuli to a patient's heart andfor guiding and supporting the OTW delivery of elongate treatmentdevices within the heart can include advancing a distal end portion of apacing guidewire into a patient's left ventricle such that first andsecond electrodes are positioned against or near a ventricular wall.Electrical stimuli can be transmitted through the guidewire to the firstand second electrodes to induce and maintain cardiac ventriculartachycardia. In various examples, the electrical stimuli transmittedthrough the guidewire can result in a current flow of 4.0 mA or less,3.0 mA or less, 2.5 mA or less, or 2.0 mA or less between theelectrodes. While the heart is in a state of ventricular tachycardia, amedical procedure, such as dilatation balloon expansion within a nativeaortic or mitral valve, can be performed.

These and other examples and features of the present pacing guidewiresand methods will be set forth, at least in part, in the followingDetailed Description. This Overview is intended to provide non-limitingexamples of the present teachings—it is not intended to provide anexclusive or exhaustive explanation. The Detailed Description below isincluded to provide further information about the present guidewires andmethods.

BRIEF DESCRIPTION OF THE DRAWINGS

In the drawings, like numerals can be used to describe similar featuresand components throughout the several views. The drawings illustrategenerally, by way of example, but not by way of limitation, variousembodiments discussed in this patent document.

FIG. 1 is a schematic illustration of the implantation of a prostheticaortic heart valve using a conventional guidewire and a dedicated rightventricular lead pacing means.

FIG. 2 is a schematic illustration of an example pacing guidewireconfigured to transmit electrical stimuli from an external pulsegenerator to the heart and guide and support the OTW delivery ofelongate treatment devices.

FIG. 3 is an enlarged schematic illustration of a proximal end portionof an example pacing guidewire.

FIG. 4 is a schematic illustration of an example connector body, whichis removably couplable to a proximal end portion of a pacing guidewire.

FIGS. 5-8 are enlarged schematic illustrations, in longitudinalcross-section, of intermediate portions of example pacing guidewires.

FIGS. 9-14 are enlarged schematic illustrations of distal end portionsof example pacing guidewires.

FIG. 15 is a schematic illustration of an example electrical connectionbetween two structures forming an elongate conductor, such as theelectrical connection at portion labeled 15 of the pacing guidewire ofFIG. 10.

FIG. 16 is a schematic illustration of an example insulationconfiguration to electrically isolate first and second elongateconductors, such as the insulation configuration at portion labeled 16of the pacing guidewire of FIG. 10.

FIGS. 17-19 are enlarged schematic illustrations of example electrodeconfigurations designed to stimulate heart tissue.

FIG. 20 is a schematic illustration of an example pacing guidewirepositioned within a left ventricle of a heart.

FIG. 21 is a graph illustrating invasive blood pressure (top), anintracardiac electrocardiogram (middle), and pacing spikes (bottom)during rapid left ventricular pacing of a pig's heart using an examplepacing guidewire.

FIG. 22 is a diagnostic image illustrating an example pacing guidewiresupporting the delivery of a heart valve system.

FIG. 23 is a schematic illustration of the implantation of a prostheticaortic heart valve using an example pacing guidewire and an externalpulse generator.

The drawing figures are not necessarily to scale. Certain features andcomponents may be shown exaggerated in scale or in schematic form, andsome details may not be shown in the interest of clarity andconciseness.

DETAILED DESCRIPTION

Definitions:

Certain terms are used throughout this patent document to refer toparticular features or components. As one skilled in the art willappreciate, different people may refer to the same feature or componentby different names. This patent document does not intend to distinguishbetween components or features that differ in name but not in function.For the following defined terms, certain definitions shall be appliedunless a different definition is given elsewhere in this patentdocument.

The terms “proximal” and “distal” refer to a position or directionrelative to a treating physician. “Proximal” and “proximally” refer to aposition that is closer to, or in a direction toward, the physician.“Distal” and “distally” refer to a position that is distant, or in adirection away, from the physician and opposite the proximal direction.

The term “patient” refers to mammals and includes both humans andanimals.

The singular forms “a”, “an”, and “the” include plural referents unlessthe content clearly dictates otherwise. As used in this specificationand the appended claims, the term “or” is generally employed in itssense including “and/or” unless the content clearly dictates otherwise.

All numeric values are assumed to be modified by the term “about,”whether or not explicitly indicated. The term “about” refers to a rangeof numbers that one of skill in the art would consider equivalent to therecited value (e.g., having the same function or result). In manyinstances, the term “about” can include numbers that are rounded to thenearest significant figure.

The recitation of numerical ranges by endpoints includes all numbers andsub-ranges within and bounding that range (e.g., 1 to 4 includes 1, 1.5,1.75, 2, 2.3, 2.6, 2.9, etc. and 1 to 1.5, 1 to 2, 1 to 3, 2 to 3.5, 2to 4, 3 to 4, etc.).

Existing Transfemoral TAVI, TAVR, BV and TMVR Procedures:

FIG. 1 is a schematic illustration of a prosthetic aortic heart valve102 being implanted into a heart 104 using a conventional guidewire 106.The heart 104 includes a right atrium 110, a left atrium 112, a rightventricle 114 and a left ventricle 116. The left ventricle 116 connectsto a body's arteries by way of an aortic valve 118 and an ascendingaorta 120. As part of the valve implantation procedure, the guidewire106 can be inserted through a guide catheter that extends from a femoralartery 122, through the ascending aorta 120, and within the aortic valve118 of the patient. The guidewire 106 can be advanced through the guidecatheter until its distal end portion locates, or nests against, theapex 124 of the left ventricle 116. With the guidewire 106 positionedinside the heart 104 and serving as an OTW support structure for therest of the valve implantation procedure, the guide catheter can beremoved from the patient.

An introducer sheath 126 can be inserted over the guidewire 106 and intothe ascending aorta 120, and subsequently a balloon catheter 128 havinga dilatation balloon 130 on its distal end portion can be passed overthe guidewire and through the sheath. A physician can locate a distaltip 132 of the introducer sheath 126 using a radiopaque marker(s) 134and fluoroscopy, or using other imaging systems such as transesophagealecho, transthoracic echo, intravascular ultrasound imaging (IVUS), or aninjectable dye that is radiopaque. The dilatation balloon 130 can beexpanded radially outward into contact with native aortic valve leaflets136 as part of a BV procedure. With information concerning the size ofthe particular aortic valve 118, the balloon 130 can be chosen so thatit expands outward and nominally compresses the aortic valve leaflets136 against surrounding aortic walls 138.

The physician or operating room staff can then crimp the expandableprosthetic aortic heart valve 102 over the dilatation balloon 130.Currently, there are two primary expandable prosthetic heart valves 102available in the U.S. to select from—the Edwards-Sapien™ heart valve(Edwards Lifesciences, Irvine, Calif.) and the CoreValve™ device(Medtronic, Minneapolis, Minn.). The Edwards-Sapien is a tri-leafletbovine pericardial valve within a tubular balloon expandable stent. Bothretrograde (i.e., transfemoral) and antegrade (i.e., transapical)approaches can be used depending on patient characteristics. TheCoreValve is a tri-leaflet porcine pericardial valve with aself-expanding nitinol stent. This valve can be used via a retrogradeapproach via transfemoral, subclavian, axillary or direct aortic access.

With the prosthetic heart valve 102 crimped over the balloon 130, thephysician can once again advance the balloon catheter 128 over theguidewire 106 and through the introducer sheath 126 until the prostheticheart valve is located at the aortic annulus between the native aorticleaflets 136. When the physician is satisfied with the positioning androtational orientation of the prosthetic heart valve 102, the balloon130 can be expanded into gripping contact with the aortic annulus. Theterm “gripping contact” can imply sufficient contact to ensure that theprosthetic heart valve 102 does not migrate after expansion. Once thevalve 102 is properly implanted, the physician can deflate the balloon130 and withdraw the balloon catheter 128 over the guidewire 106. Theintroducer sheath 126 can then be withdrawn simultaneously with, orfollowed by, the guidewire 106.

During existing TAVI, TAVR, BV and TMVR procedures, temporary rightventricular rapid pacing 108, which has been associated with a small butrecognized rate of morbidity, is performed in order to induce andmaintain a ventricular tachycardia. The ventricular tachycardia canlower the patient's blood pressure to allow balloon deployment in theaortic annulus without balloon embolization from cardiac flow, and itcan assure more accurate placement of the prosthetic heart valve 102being implanted. The traditional way of temporary pacing involves afemoral or jugular venous puncture to place the distal end portion of aunipolar pacing lead 140 in or on a wall of the right ventricle 114. Aproximal end portion of the lead 140 can be connected to a first pole ofan external pulse generator 142 with an alligator clamp, and a secondopposite pole of the external pulse generator 142 can be electricallyconnected to a large surface skin electrode 144 placed at a left thigh146 of the patient, for example. The skin electrode 144 can be used as areturn electrode for the single lead electrode.

In an effort to streamline TAVR and other valve-related procedures andavoid attendant complications, the present inventors have investigateduse of a 0.035 in (0.89 mm) left ventricular delivery wire as a pacinglead. Though this concept is conceptually appealing, in practice the useof guidewires for pacing is challenging since existing wires are notinsulated against current loss in blood and therefore: cannot be testedfor ventricular capture until they are insulated within a patient's bodysuch as with a valvuloplasty balloon or a TAVR device; cannot provideobligate pacing following TAVR without the valvuloplasty balloon or TAVRdevice left in place; can only provide unipolar pacing in conjunctionwith a grounding contact in or on subcutaneous tissue and anon-dedicated connection to an electrical source; and have high pacingcapture thresholds and low safety margins due to unipolar pacing.

The guidewires and methods disclosed in this patent document include apurpose built rail device with insulated poles capable of consistentleft ventricular pacing at low thresholds with or without a deliverysystem (e.g., a valvuloplasty balloon or a TAVR device) in place. Thepacing guidewires and related methods can improve procedural safety andefficiency by providing the dual purpose of (i) transmitting electricalstimuli to the heart 104 for inducing and maintaining a ventriculartachycardia, and (ii) guiding and supporting the OTW delivery ofelongate treatment devices (e.g., a balloon catheter) for successfulimplantation of the prosthetic aortic heart valve 102. It is believedthat pacing the heart 104 using a left ventricular bipolar guidewire canbe a beneficial alternative to conventional transvenous temporary rightventricular pacing 108 in the context of TAVI, TAVR, BV and TMVRprocedures. Among other things, this pacing alternative obviates theneed for an additional venous puncture and avoids the cost, discomfort,and risk of perforating the right ventricle 114 with the temporaryunipolar pacing lead 140.

In the description that follows, the present pacing guidewires are shownas having a design that is optimized for use in connection with TAVI,TAVR or BV procedures. For example, a guidewire can be designed with asufficient degree of flexibility to facilitate negotiation of tortuousanatomy and to minimize trauma to cardiac tissue, while also maintaininga certain level of stiffness, particularly in the aortic valve region,in order to provide adequate support for items delivered thereon (e.g.,aortic valve implantation systems) and to sit comfortably within theleft ventricle 116 in a stable, atraumatic manner. It should be noted,however, that the present pacing guidewires are not limited to use inTAVI, TAVR and BV procedures. The guidewires could be similarly utilizedin a wide variety of percutaneous medical procedures, such asgastrointestinal or hepatobiliary procedures, as well as alternativetypes of coronary procedures such as TMVR, without departing from thescope of the present patent document.

Pacing Guidewires of Present Subject Matter:

FIG. 2 is a schematic illustration of a pacing guidewire 248 includingan elongate body 250 carrying a first elongate conductor 252, a secondelongate conductor 254, and at least two electrodes 256, 258 fordelivering electrical stimuli to a heart, such as to a left ventricle ofthe heart. Portions of the elongate body 250 can include a lubriciouscoating (e.g., a coating including hydrophilic, polytetrafluoroethylene(PTFE), silicone or other dry lubricious material) to ease itsadvancement through a guide catheter and to facilitate the OTW deliveryand withdrawal of devices guided over it. In an example, a first portionof the elongate body 250 has a silicone coating and a second portion ofthe body has a hydrophilic coating. The coating(s) can be applied by dipcoating, spraying, or shrink wrapping a hollow tube of such materialover the outer surface of the elongate body 250.

Indicia suitable for viewing by a physician, thereby providing adistinguishing characteristic from non-pacing guidewires and otherinterventional tools that may be used during a procedure, can be appliedto the coating(s) or the elongate conductors 252, 254. The indicia canbe applied to the coating(s) before or after their application to theelongate body 250. Alternatively, the indicia can be applied to theconductors 252, 254 and a transparent or light-colored coating can beapplied over the conductors for visibility of the darker indicia. Theindicia can include one or more continuous helical strips, individualdiscontinuous circumferential stripes, or other axially spaced apartindicia along the length of the guidewire. The indicia can be bi-color,tri-color, or any combination of colors that are discernable. Theindicia can be about 1 mm to 4 mm wide and spaced apart by a similardistance for clarity. The indicia can extend over the entire length ofthe elongate body 250 or solely over a certain portion(s) of the length.

The elongate body 250 can extend from a proximal end portion 260 to adistal end portion 262, with an intermediate portion 264 therebetween.The proximal end portion 260 can be manipulated by the physician from aposition outside of a patient's body. The distal end portion 262 caninclude a flexible tip to facilitate traversal through the body to oneor more target pacing sites. The elongate body 250 can have any suitablelength for use in conducting electrical stimuli from an external pulsegenerator 242 to the heart of the patient, such as from about 100 cm toabout 300 cm. The elongate body 250 can have a circular cross-sectionfor facilitated insertion through portions of the body. The diameter ofthe elongate body 250, including insulation, can be in the range ofabout 0.014 in (0.36 mm) to about 0.038 in (0.97 mm), such as about0.035 in (0.89 mm), although other sizes are also possible.

The first and second conductors 252, 254 allow the guidewire 248 tofunction as a bipolar pacing wire. The first conductor 252 can extendlongitudinally from a terminal contact at a proximal end portion 266,through or along the elongate body 250, to a distal end portion 268electrically connected to at least the first electrode 256. The secondconductor 254 can similarly extend longitudinally from a terminalcontact at a proximal end portion 270, through or along the elongatebody 250, to a distal end portion 272 electrically connected to at leastthe second electrode 258. Each conductor 252, 254 can be formed of asingle structure or multiple structures, which are electrically joinedtogether such as by soldering or welding. The conductors 252, 254 can behighly flexible small diameter metal filaments, stranded cables, helicalcoils constructed of circular wire or flat wire (allowing fordiametrical space savings), corewires, braids, hypotubes orelectrically-conductive polymer layers constructed from a conductive,low resistance material, such as MP35N® alloy (SPS Technologies,Jenkintown, Pa.), Elgiloy® alloy (Elgiloy Specialty Metals, Sycamore,Ill.), tungsten, platinum, silver, stainless steel, polyacetylene orcombinations thereof, for example.

The first and second electrodes 256, 258 can be coaxially oreccentrically mounted along the elongate body 250 and can spaced apartby a predetermined distance, such as a distance between about 1 cm and10 cm, with insulation in between. In some examples, more than twoelectrodes—such as three, four or five electrodes—can be mounted alongthe elongate body 250. The electrodes 256, 258 can be cylindrical inshape and can have an axial length between about 2 mm and about 20 mm,for example, for delivery of electrical stimuli to the heart. At leastone electrode can serve as the anode and at least one other electrodecan serve as the cathode. The present inventors have found that limitingthe collective axial length of cylindrical electrodes of each polarityto 12 mm or less, and particularly 10 mm or less, can provide abeneficial, more concentrated current density to heart tissue. Forexample, if the second conductor 254 is electrically connected to threecylindrical electrodes, the collective axial length of those threeelectrodes can be 12 mm or less, or 10 mm or less. Alternatively, one ofboth of the electrodes 256, 258 can have a non-cylindrical, strip-like(channel-like) shape axially extending for lengths between about 1 cmand 10 cm, for example. Each electrode can be made up of one strip ormultiple strips. The strip(s) can be straight and extend along one sideof the guidewire or can have a spiral configuration that wraps aroundthe guidewire.

In operation, AC stimuli signals created by the external pulse generator242 can be applied to the electrodes 256, 258. The pulse generator 242can include means for delivering time-spaced pulses to the electrodes256, 258 for suitable pacing. Current on the order of about 4.0 mA orless, 3.0 mA or less, 2.5 mA or less, or 2.0 mA or less, for example,can flow through blood or other fluid between the spaced apartelectrodes 256, 258.

FIG. 3 is an enlarged schematic illustration of a proximal end portion360 of an example pacing guidewire's elongate body 350. In this example,a first conductor 352 can be at least partially in the form of acorewire, and a second conductor 354 can be at least partially in theform of a braid or hypotube. Each conductor 352, 354 can include adedicated terminal contact brought out from the elongate body 350 at itsproximal end portion 366, 370. The terminal contacts can be in-line withone another for direct electrical connection with an external pulsegenerator 342 via a generator receptacle 371, or indirect electricalconnection with the pulse generator 342 via a dedicated connector body.Any other suitable method of effecting electrical connection between theconductors 352, 354 and the pulse generator 342 can also be employed.

FIG. 4 is a schematic illustration of an example connector body 474removably couplable to a proximal end portion of a pacing guidewire'selongate body. The connector body 474 can include a guidewire connectionportion 475 and pulse generator connection portions 477 a, 477 b. Theguidewire connection portion 475 can be slid on and off the proximal endportion of the pacing guidewire's elongate body and can include anentrance seal member to electrically isolate conductors of the pacingguidewire from bodily and medical fluids present in the treatment area.The pulse generator connection portions 477 a, 477 b can provide anelectrical extension of the guidewire's conductors and can becolor-coded or otherwise marked for identification of each conductor'spolarity. In this example, pulse generator connection portion 477 a hasa negative polarity (cathode) and pulse generator connection portion 477b has a positive polarity (anode). The pulse generator connectionportions 477 a, 477 b can make electrical connections with the pulsegenerator by way of alligator clips, for example.

FIGS. 5-8 are enlarged schematic illustrations, in section, ofintermediate portions 564, 664, 764, 864 of an example pacingguidewire's elongate body 550, 650, 750, 850. The elongate body 550,650, 750, 850 can include one or more tapers and constant diameterregions, which can be manifested in variations in the size of the outerdiameter, the inner diameter and the wall thickness of body components.Any tapers and constant diameter regions can be formed by any one of anumber of different techniques, for example, by centerless grindingmethods, stamping methods, extrusion methods, co-extrusion methods, andthe like.

A corewire 580, 680, 780, 880 can extend from a proximal end portion toa distal end portion of the elongate body 550, 650, 750, 850. Thecorewire can have a gradual reduction (or taper) 582, 682, 882 in itscross-sectional diameter through the intermediate portion 564, 664, 864,as shown in the examples of FIGS. 5, 6 and 8. This gradual reduction582, 682, 882 can provide the elongate body 550, 650, 850 with adiminishing degree of stiffness and increased flexibility towards itsdistal end portion. By enhancing its flexibility, the distal end portionof the elongate body 550, 650, 850, which can be designated forplacement against sensitive myocardial tissues and structures, is lesslikely to impart potentially harmful forces. At the same time, theintermediate portion 564, 664, 764, 864 can maintain an adequate degreeof stiffness to support the OTW delivery of critical components, such asa dilatation balloon or a prosthetic aortic valve.

The transition in cross-sectional diameter along the corewire 580, 680,880 can be provided in a subtle manner to render the guidewire moreresistant to kinking upon the application of stress. The presentinventors have found that regions in a corewire with rapid transitionsin cross-sectional diameter are more susceptible to the formation ofsharpened bends or kinks during use. The creation of sharpened bends orkinks in the corewire can be problematic in that they can introducetraumatic forces against a point on a ventricular wall, for example,thereby perforating or otherwise damaging heart tissue, and can catch ona device slidably mounted over the guidewire.

As shown in the examples of FIGS. 5-7, the corewire 580, 680, 780 can bemade from an electrically-conductive material and, as such, can at leastpartially form one of the guidewire's conductors 552, 652, 752, whilethe second of the guidewire's conductors 554, 654, 754 can surround aportion of the corewire and can take the form of a helical coil 584(FIG. 5), an electrically-conductive polymer layer 686 (FIG. 6), ahypotube 788 (FIG. 7), a braid or a combination thereof.

In the example of FIG. 5, the helical coil 584 can be secured to thecorewire 580 at each of its ends using a bonding agent, such as anelectrically-insulating, non-conductive epoxy, but otherwisefree-floating relative to the corewire 580. The helical coil 584 can bea single filar coil or a multi-filar coil.

In the example of FIG. 6, the electrically-conductive polymer 686 can beof tubular form or alternatively in the form of a tape that is helicallywrapped about the corewire 680. Conductive polymers fall into twogeneral categories: intrinsically conductive and conductor-filled.Intrinsically conductive polymers can include polyacetylene, polypyrroleand polyaniline, among others. Alternatively, conductor-filled polymerscan include presently available materials approved for implantation suchas silicone rubber with embedded metallic, carbon or graphite particlesor powder.

In the example of FIG. 7, the corewire 780 can be concentric and slideinside the hypotube 788. This design can enable a proximal electrode tobe placed at a desired location, and a distal electrode can be extendeda variable distance beyond the proximal electrode.

As shown in the example of FIG. 8, the corewire 880 can be electricallyneutral and at least partially surrounded by first and second conductors852, 854 in the form of helical coils 884 a, 884 b. Two conductive wirescan be in coaxially wound into a single helical form. The wires can beinsulated from one another prior to winding and can optionally be ofdiffering diameters, as shown in the example of FIG. 17. Alternatively,a first conductor can be wound into a helical coil of a diameter lessthan a winding of a second conductor.

The helical coil(s) 584, 884 a, 884 b, electrically-conductive polymerlayer 686, or hypotube 788 can extend a substantial length of thecorewire 580, 680, 780, 880 or can extend solely around its proximalend, intermediate 564, 664, 764, 864, and/or distal end portions. Thepresent inventors have found that helical coils extending the entirelength of the corewire require electricity to travel a relatively longdistance and can increase the electrical resistance associated with anelectrical path between an external pulse generator anddistally-positioned electrodes. Accordingly, a low resistance linearfilament, stranded cable, hypotube, or braid can be used to travel aportion of the length of the corewire and bridge the electrical pathbetween the external pulse generator and an intermediate- ordistally-positioned helical coil portion acting as an electrode, forexample.

An insulative sheath or other member 594, 694, 794, 894 comprisingnon-conductive material can be disposed about the outer surface of thecorewire 580, 680, 780, 880, helical coil(s) 584, 884 a, 884 b,electrically-conductive polymer layer 686, hypotube 788, or braid toelectrically insulate the components from one another and fromsurrounding body tissue when implanted. Suitable materials for theinsulative sheath or other member 594, 694, 794, 894 can include medicalgrade polymers, such as silicone and polyurethane, which can beengineered to create a desired degree of flexibility for bending duringsurgery. Suitable materials can also have a low coefficient of friction,such as PTFE, polyperfluoroalkoxy (PFA), fluorinated ethylene-propylene(FEP), polyethylenechlorotrifluoro-ehtylene (ECTFE), silicone rubber,polyurethane, and styrene-ethylene-butylene-styrene block polymer.

FIGS. 9-14 are enlarged schematic illustrations of distal end portions962, 1062, 1162, 1262, 1362, 1462 of an example pacing guidewire'selongate body 950, 1050, 1150, 1250, 1350, 1450. The distal end portionof the elongate body can have a preformed shape 990, 1090, 1190, 1290,1390, 1490, such as a pigtail shape (FIGS. 9-11), a J-shape (FIGS. 12and 13), a V-shape (FIG. 14) or other non-linear shape, prior to surgeryto provide a relatively long, gentle bend that limits the risk of damageto delicate tissue (e.g., vessel walls, aortic or mitral valves, orventricular walls) during introduction and positioning of the guidewirewithin a patient or to provide a region to conform to anatomical shapes(e.g., the ventricular apex). A prearranged loading tool can be includedwith the guidewire for straightening and facilitating introduction ofits distal end portion into a guide catheter. As will be appreciated,the introduction of an elongate resilient bend can minimize thelikelihood of trauma to the patient by transmitting forces applied tocardiac tissues and structures by the guidewire along a dispersed,radial path rather than along a concentrated, longitudinal path via theguidewire's tip. The looping bend can also provide for a longertransition between the stiff support section of the guidewire and thesofter atraumatic distal end portion. In an example, the distal endportion has relatively enhanced flexibility and low tip stiffness (e.g.,1 g, 2 g, 3 g, 4 g or 5 g) such that the preformed shape can instantlycurve into its unbiased shape upon discharge from the guide catheter.

To form the preformed biased shape 990, 1090, 1190, 1290, 1390, 1490, acorewire, a surrounding conductor, or both, can be constructed of asuperelastic material, such as a nickel-titanium alloy, and can bemanufactured in the biased shape to thus bias the elongate body 950,1050, 1150, 1250, 1350, 1450. The distal end portion of the corewire,the surrounding conductor, or both, can optionally be shaped during athermal shape setting process. As part of the process, the distal endportion(s) can be inserted into a sleeve that is shaped into a desiredconfiguration. Heat can then be applied to the distal end portion(s)through the sleeve for a period of time. Once cooled and removed fromthe sleeve, the corewire, the surrounding conductor, or both, can bepermanently imparted with the desired shape. Accordingly, although theelongate body 950, 1050, 1150, 1250, 1350, 1450 can be reconfigured uponapplying a suitable force thereon (e.g., straightened during insertionthrough a guide catheter), the thermal treatment of the corewire, thesurrounding conductor, or both, can cause the distal end portion of theelongate body to resiliently return to its preformed configuration inthe absence of forces.

As shown in the examples of FIGS. 9-14, first and second electrodes 956,958, 1056, 1058, 1156, 1158, 1256, 1258, 1356, 1358, 1456, 1458 can bespaced apart along, and supported by, the preformed shape 990, 1090,1190, 1290, 1390, 1490. Optionally, as shown in the example of FIG. 10,third and fourth electrodes 1059, 1061 can also be spaced along thepreformed shape 1090 and can have the same polarity as the secondelectrode 1058 (via connection to the same conductor). The addition ofthe third and fourth electrodes 1059, 1061 can increase the likelihoodof electrode contact with heart wall tissue.

The pigtail shape 990, 1090, 1190 of FIGS. 9-11 can have a side height982, 1082, 1182 of between about 20 mm-40 mm, can turn through more than270 degrees, more than 360 degrees or more than 540 degrees, and can becomposed of a corewire and one or more helical coils, for example. Thepresent inventors have found that multiple nested loops (e.g., a firstloop within a second loop) make it even less likely that the distal endportion of the guidewire can cause trauma to bodily tissue during itspositioning. The corewire can be made from an electrically-conductivematerial and, alone or in combination with a first helical coil or otherstructure, can form one of the guidewire's elongate conductors. Forexample, as shown in FIG. 15, a corewire 1580 can be electricallycoupled to a first helical coil or first helical coil portion 1584 a toform an elongate conductor. A second helical coil or second helical coilportion can surround a portion of the corewire and, alone or incombination with another structure(s) (e.g., hypotube and/or braid), canform the second of the guidewire's conductors. As shown in FIG. 16,first and second helical coils or helical coil portions 1684 a, 1684 bcan be longitudinally separated by a coil insulator 1679 positionedbetween a guidewire's two electrodes having opposite polarities.

Each helical coil or helical coil portion can include one or more filarsand can be constructed from an appropriate formable material, such asbut not limited to stainless steel, that is surrounded by insulationoptionally applied with a lubricious coating on its exterior surface tofacilitate advancement and retraction of the guidewire through the guidecatheter. The use of a stainless steel material to form the helicalcoils can render them radiolucent. Accordingly, a portion of the helicalcoils can be applied with a radiopaque surface treatment (e.g., aplatinum, palladium, gold, tantalum, or tungsten-based treatment) torender them highly visible under fluoroscopy.

The pigtail shape 990, 1090, 1190 of FIGS. 9-11 can optionally have agradual reduction in cross-sectional diameter toward its distal end, andthe radius of curvature of the pigtail shape can also decrease towardthe distal end. This can provide a resulting pacing guidewire that hasadequate stiffness to be inserted into a heart and provides support foritems delivered OTW (e.g., aortic valve implantation systems), whilealso having flexibly and resilience so that it can maintain at least oneelectrode in contact with a ventricular wall in the presence of factorssuch as the beating of the heart and patient movement, both of which caninterrupt engagement between an electrode and the ventricular wall.

The preformed shape of the distal end portion of the guidewire'selongate body need not be constructed as a single plane structure.Rather, since the space within the left ventricle is multi-planar, thepreformed shape 1390 of the distal end portion 1362 can be constructedas a multi-planar structure, as shown in FIG. 13. The distal end portion1362 can be non-coplanar relative to adjacent distal end portions orrelative to the proximal or intermediate portions of the elongate body.In an example, the distal end portion 1362 is disposed at an angle 1392relative to a plane containing the central axis of an intermediateportion 1364 of the elongate body, where the angle is between about 2degrees and about 30 degrees.

FIGS. 17-19 are enlarged schematic illustrations of example electrodeconfigurations designed to contact and stimulate heart tissue. A distalend portion 1762, 1862, 1962 of an elongate body 1750, 1850, 1950 can beprovided with at least first and second electrodes 1756, 1758, 1856,1858, 1956, 1958 spaced apart by an insulative sheath or other member1794, 1894, 1994. The electrodes 1756, 1758, 1856, 1858, 1956, 1958 canbe electrically connected through or along the elongate body 1750, 1850,1950 by first and second conductors to the proximal end portion of theelongate body. In an example, the first electrode 1756, 1856, 1956 canbe provided at or near the distal end portion of the guidewire, and thesecond electrode 1758, 1858, 1958 can be spaced rearward (or moreproximal) from the first electrode. Each electrode can beneficially beformed of platinum, carbon, iridium or titanium, for example, and itssurface can optionally be treated using chemical, mechanical, orelectrical and mechanical methods to improve resistance to polarizationor decrease the stimulation threshold. One or both electrodes can beradiopaque to assist in fluoroscopic location of the measurement site.

It is within the contemplation of the present pacing guidewires thatthere be no separate electrode structure and an exposed surface of aconductor in which the insulative sheath has been removed can be anelectrode. The insulative sheath can be removed about the entirecircumference of the conductor, forming a ring-shaped electrode surface,or only a portion of the insulative sheath can be removedcircumferentially about the conductor, forming a semi-ring shapedelectrode surface. Exposing a length of a conductor to allow it to bethe electrode has the advantage of eliminating a connection between aseparate electrode structure and the conductor.

In the example of FIG. 17, first and second conductors 1752, 1754 in theform of helical coils 1784 a, 1784 b of differing diameters andinsulated from one another prior to winding are shown. The firstconductor 1752 can extend more distal than the second conductor 1754 andcan electrically connect to a first electrode 1756. The first electrode1756 can comprise a cup-shaped element defining the leading tip of theguidewire. A portion(s) of the insulation covering the second conductor1754 can be removed to form second, more proximal electrode(s) 1758. Inembodiments where multiple electrode contacts are connected to the sameconductor, the electrode with the best tissue contact, as determined bya pacing system analyzer (PSA), can serve as the stimulating electrode.This configuration can allow for a decrease in stimulation threshold.

Alternatively, as shown in the example of FIG. 18, a second, moreproximal electrode 1858 can comprise a ring electrode spaced from afirst, more distal electrode 1856. The electrical connection between asecond conductor 1854 and the ring electrode can be by means of a crimpring. The crimp ring can have a length approximately one-half the axiallength of the ring electrode. In effecting the connection of the secondconductor 1854 to the second electrode 1858, the distal end portion ofthe conductor can be brought out from the guidewire at a point adjacentthe distal end of the crimp ring. The conductor 1854 can be folded backtoward the proximal end portion of the guidewire. The electrode 1858 canthen be slipped over the guidewire and the crimp ring can clamp the endof the conductor 1854 therebetween. Upon installation of the electrode1858, the assembly can be dipped in a suitable adhesive material to fillthe bore from which the conductor 1854 may be removed in bringing itsdistal end portion outwardly from the guidewire. The electrode 1858 canbe formed with connector elements on its inner surface to receive thedistal end portion of the conductor in a variety of other ways as well.

In the example of FIG. 19, an outer surface of each of first and secondelectrodes 1956, 1958 can be raised beyond an outer surface of theelongate body 1950. Electrodes designed in this fashion can increase thechances of achieving intimate tissue-electrode contact resulting inlower pacing thresholds.

Interplay of Example Pacing Guidewire and Heart:

FIG. 20 is a schematic illustration of an example pacing guidewire 2048positioned within a left ventricle 2016 of a heart 2004. In thisposition, the guidewire 2048 can provide good support for the OTWdelivery of elongate aortic valve treatment devices and can provideelectrical stimuli to the left ventricle 2016 to induce and maintaincardiac ventricular tachycardia during medical procedures such as TAVI,TAVR and BV.

The guidewire 2048 can include an elongate body 2050 having anintermediate portion 2064 positioned within an aortic valve 2018 and adistal end portion 2062 extending into the left ventricle 2016. Thedistal end portion 2062 can conceptually be separated into a firstregion 2096 configured to contact a ventricular wall 2001 on a firstside of a ventricular apex 2003, a second region 2097 configured to spanacross the apex 2003, a third region 2098 configured to contact aventricular wall 2005 on a second side of the apex 2003, and/or a fourthregion 2099 configured to curve away from the ventricular wall 2005 onthe second side of the apex 2003.

Electrode means conductively connected to the distal end portion 2062 ofthe elongate body 2050 can provide low resistant and low impedanceelectrical interfaces with bodily fluid and excitable tissue in contactwith, or in the vicinity of, the electrode means. In the example shown,a first electrode 2056 is disposed on the fourth region 2099, a secondelectrode 2058 is disposed on the third region 2098, a third electrode2059 is disposed on the second region 2097, and a fourth electrode 2061is disposed on the first region 2096. The second, third and fourthelectrodes 2058, 2059, 2061 can have an opposite polarity as the firstelectrode 2056, and collectively, these electrodes can serve as thepositive and negative poles during pacing and can be maintained in goodelectrical contact with the walls of the left ventricle 2016 directly orindirectly via blood or other fluid. By way of example, the firstelectrode 2056 can serve as the anode, and the second, third and fourthelectrodes 2058, 2059, 2061 can serve as the cathode. The presentinventors have found that advantageous (low) capture and pacingthresholds can be achieved when at least the cathode is in direct ornear direct contact with heart tissue (e.g., wall tissue of the leftventricle).

Temporary Pacing Laboratory Tests and Animal Trials:

The energy transmission to the heart provided by two electrodespositioned within a left ventricle was investigated not only inlaboratory tests, but also in practical animal trials.

First Animal Trial:

Temporary pacing of a pig's heart using two electrodes positioned in theleft ventricle was successfully performed with a fraction of the energyrequired to capture and pace the heart relative to using conventionaltemporary pacing, which, as shown in FIG. 1, involves a femoral orjugular venous puncture to place a unipolar pacing lead (firstelectrode) in a right ventricle and a second electrode on a patient'sskin.

The present inventors also discovered that substantially less energy isrequired to pace a pig's heart using two electrodes positioned in theleft ventricle relative to using a first electrode positioned at theskin's surface or in the aorta and a second electrode positioned in theleft ventricle, as the following findings show.

Capture Negative Pole Positive Pole Threshold Guidewire having a fullyElectrode pad on back 7 mA exposed pigtail at its distal end portionpositioned in left ventricle Guidewire having a fully Electrode clampattached 5.5 mA exposed pigtail at its to skin near femoral distal endportion access point positioned in left ventricle Guidewire having afully Electrode needle in chest 3.5 mA exposed pigtail at its distal endportion positioned in left ventricle Guidewire having a fully Guidewirehaving a 4.0 mA exposed pigtail at its partially exposed straight distalend portion distal end portion positioned in aorta positioned at apex inleft ventricle Guidewire having a Guidewire having a 3.5 mA partiallyexposed pigtail partially exposed straight at its distal end portiondistal end portion positioned in aorta positioned at apex in leftventricle Guidewire having a Pacing lead having a 0.3 mA partiallyexposed straight distal electrode distal end portion positioned at apexin left positioned in left ventricle ventricle with no ventricular wallcontact

Second Animal Trial:

Three embodiments of the present bipolar pacing guidewire were testedfor capture threshold in two different locations—the apex and mid-leftventricle—within a pig's heart. Rapid pacing ability and functionalityduring inflation of a 20 mm Edwards-Sapien™ 3 heart valve deliverysystem (Edwards Lifesciences, Irvine, Calif.) were also tested. Theprimary objective was to demonstrate consistently acceptable rapidpacing capture thresholds and persistent pacing induced hypotensionunder a series of unique conditions and positions. Capture thresholdswere evaluated with pacing guidewires positioned in the left ventricularapex and mid-cavity at a rate of 130 bpm using both positive andnegative polarity at the distal node. Rapid pacing ability was confirmedat 180 bpm with balloon inflation.

Using the bipolar pacing guidewires, capture thresholds were 1.2+/−0.36mA when the wire was positioned at the left ventricular apex and1.75+/−0.25 mA when the wire was positioned in the left ventriclemid-cavity, out of contact with the apex. Rapid pacing at 180 bpm wasthen successfully achieved with all pacing guidewires at 2× capturethreshold (FIG. 21). The Edwards-Sapien™ 3 heart valve delivery systemwas subsequently introduced and re-confirmed consistent rapid pacingability at 2× capture threshold during delivery system inflation (FIG.22).

As a control, unipolar left ventricular pacing was tested in a secondpig model using an Amplatz Super Stiff guidewire (Boston ScientificCorporation, Boston, Mass.) and ground using a 22 gauge needle insubcutaneous tissue. The guidewire was insulated with a 5 French AR1diagnostic catheter. Capture threshold testing was repeated in themid-cavity and left ventricular apical positions and rapid pacing at 180bpm.

In the control arm, capture thresholds were 6.0 mA and 5.0 mA with theAmplatz Super Stiff guidewire in the mid-cavity and left ventricularapical positions, respectively. Rapid pacing at 180 bpm was alsoconfirmed at 2× capture threshold in both positions.

Transfemoral TAVI, TAVR and BV Procedures Using Example PacingGuidewire:

FIG. 23 is a schematic illustration of a prosthetic aortic heart 2302valve being implanted using an example pacing guidewire 2348, and anoptional closed loop external pulse generator 2342. The guidewire 2348can be designed as both an OTW delivery wire (e.g., to reliably guideaortic valve delivery systems and implants to a desired site) and abipolar pacing means, thereby obviating the need for a dedicated rightventricular pacing system, which has been conventionally used and isillustrated in FIG. 1. The guidewire 2348 can be a one-time usedisposable device and a proximal connector body can be designed to becompatible with a reusable external pulse generator 2342.

As part of the valve implantation procedure, the guidewire 2348 can beinserted through a guide catheter that extends from a femoral artery2322, through an ascending aorta 2320, and within the aortic valve 2318of a patient. The guidewire 2348 can be advanced through the guidecatheter until its distal end portion projects into a left ventricle2316 and assumes a preformed bias (e.g., pigtail) shape 2390. As shown,the guidewire 2348 can travel along an arcuate path made up of aventricular wall 2301 on a first side of a ventricular apex 2303, theventricular apex 2303, and a ventricular wall 2305 on a second side ofthe ventricular apex 2303 as it is advanced into the left ventricle. Inone example, when the guidewire 2348 is fully advanced into the leftventricle 2316, a first electrode 2356 can be positioned a spaceddistance from the ventricular wall 2305 on the second side of theventricular apex, a second electrode 2358 can be positioned against thisventricular wall 2305, and the guide catheter can be removed from thepatient.

Positioned as such within the left ventricle, the guidewire 2348 can beused to transmit electrical stimuli from the external pulse generator2342 to the first and second electrodes 2356, 2358 to induce andmaintain cardiac ventricular tachycardia, thereby resulting in reducedcardiac output to allow balloon deployment in the aortic annulus withoutembolization from cardiac flow. The electrical stimuli can besufficiently slow to capture the ventricular myocardium in a 1:1 manner,while being sufficiently fast to lower the systolic blood pressure toless than about 70 millimeters of mercury (mmHg) and the pulse pressureto less than about 20 mmHg. In some examples, the transmitted electricalstimuli can result in a current flow of 3.0 mA or less between the firstand second electrodes 2356, 2358 (during full pacing) or 1.5 mA or lessbetween the first and second electrodes 2356, 2358 (during initialcapture) and ventricular rates of 120-220 beats per minute (bpm).

Medical procedures utilizing the pacing guidewire 2348 as a delivery andsupport means can then be performed on the heart while it is maintainedin a state of ventricular tachycardia. For example, an introducer sheath2326 can be inserted over the guidewire 2348 and into the ascendingaorta 2320, with a balloon catheter 2328, having a dilatation balloon2330 on its distal end portion, passed over the guidewire 2348 andthrough the sheath 2326. A physician can locate a distal tip 2332 of theintroducer sheath 2326 using a radiopaque marker(s) 2334, for example,and the dilatation balloon can be expanded radially outward into contactwith native aortic valve leaflets 2336 as part of a BV procedure. Withinformation concerning the size of the particular aortic valve 2318, theballoon 2330 can be chosen so that it expands outward and nominallycompresses the aortic valve leaflets 2336 against the surrounding aorticwalls 2338.

The physician or operating room staff can then crimp the expandableprosthetic aortic heart valve 2302 over the dilatation balloon 2330.With the prosthetic heart valve 2302 crimped over the balloon 2330, thephysician can once again advance the balloon catheter 2328 over theguidewire 2348 and through the introducer sheath 2326 until theprosthetic heart valve 2302 is located at the aortic annulus and betweenthe native aortic leaflets 2336. When the physician is satisfied withthe positioning and rotational orientation of the prosthetic heart valve2302, the balloon 2330 can be expanded into good contact with the aorticannulus. Once the valve is properly implanted, the physician can deflatethe balloon 2330 and withdraw the balloon catheter 2328 over theguidewire 2348. The introducer sheath 2326 can then be withdrawnsimultaneously with, or followed by, the guidewire 2348.

The external pulse generator 2342 can optionally contain electronics andsoftware necessary to detect certain electrophysiological responses tothe electrical stimuli and then adjust the transmitted stimuli in aclosed loop manner (i.e., control the functioning of a heart inaccordance with information obtained about its mechanical state). Thepulse generator 2342 may be designed specifically for temporary use aspart of a system to perform TAVI, TAVR or BV in which the goal is todrop blood pressure and cardiac output below a prespecified level toallow for safe balloon deployment. When cardiac output is below theprespecified level for safe balloon deployment, an indicator light 2351on the pulse generator 2342 can change from red to green.

The electrophysiological responses can, in some examples, be detectedfrom an intra-arterial pressure monitor 2353 positioned in a centralartery 2355 using an indwelling catheter that is an existing componentof the medical procedure. Monitored pressure signals, such as systolicblood pressure or pulse pressure, can be processed using an algorithmand an electrical stimuli (pacing) rate can designed to achieve 1:1ventricular capture in most patients, such as about 120 bpm to 220 bpm,can be calculated. If the pacing rate at any point leads to less than1:1 capture of the ventricle (as monitored, for example, by therelationship between pacing frequency and systolic pressure rise), thepulse generator 2342 can decrease pacing frequency in order to capturethe ventricle in a 1:1 fashion, then re-initiate the algorithm toincrease pacing rate in order to meet the hemodynamic goals as statedabove (systolic blood pressure less than about 70 mmHg and pulsepressure less than about 20 mmHg).

CLOSING NOTES AND EXAMPLES

TAVI, TAVR, BV and TMVR procedures are occurring with increasingfrequency throughout the world. Further commercialization anddevelopment of new and alternative devices to facilitate such proceduresare only going to encourage this trend.

The present pacing guidewires and methods can minimize procedural times,obviate potential complications, and optimize outcomes in TAVI, TAVR, BVand TMVR procedures. For example, the pacing guidewires can beconfigured to provide good support for the OTW delivery of elongatetreatment devices with less chance of perforation or other damage ofvessels, the native aortic or mitral valve, or cardiac tissues throughwhich the guidewires are inserted. Pacing electrodes, by being part ofeach guidewire and insulated from one another, can minimize the stepsand risks of the valve procedures by obviating the need for anadditional venous puncture for insertion of a dedicated rightventricular temporary pacing lead and can be ready for capture tests orpacing without a delivery system in place.

Laboratory and animal trials have proven the safety and efficacy ofcardiac pacing using electrodes associated with the pacing guidewires asan alternative to the traditional approach of separate dedicatedtemporary pacing leads. The animal trials, for example, suggest capturethresholds on par with traditional temporary right ventricular pacingleads (but without the associated risks) and significantly lower capturethresholds than those seen with standard guidewires acting as a unipolarsystem in the left ventricle. Unlike standard guidewires, the presentpacing guidewires do not require insulation in the form of anover-the-wire delivery device to function, and therefore thresholdtesting can be carried out immediately after placement. Furthermore, themechanical properties of these pacing guidewires, including a pre-shapedtip, demonstrated no preliminary safety concerns during delivery of aballoon-expandable valve delivery system from a femoral artery to anative aortic valve.

The above Detailed Description includes references to the accompanyingdrawings, which form a part of the Detailed Description. The DetailedDescription should be read with reference to the drawings. The drawingsshow, by way of illustration, specific embodiments in which the presentpacing guidewires and methods can be practiced. These embodiments arealso referred to herein as “examples.”

The Detailed Description is intended to be illustrative and notrestrictive. For example, the above-described examples (or one or morefeatures or components thereof) can be used in combination with eachother. Other embodiments can be used, such as by one of ordinary skillin the art upon reviewing the above Detailed Description. Also, variousfeatures or components have been or can be grouped together tostreamline the disclosure. This should not be interpreted as intendingthat an unclaimed disclosed feature is essential to any claim. Rather,inventive subject matter can lie in less than all features of aparticular disclosed embodiment. Thus, the following claim examples arehereby incorporated into the Detailed Description, with each examplestanding on its own as a separate embodiment:

In Example 1, a method for transmitting electrical stimuli to apatient's heart and for guiding and supporting the delivery of elongatetreatment devices within the heart can comprise advancing a distal endportion of a bipolar pacing guidewire into the left ventricle such thatfirst and second electrodes are positioned against or spaced from aventricular wall. Electrical stimuli can be transmitted through theguidewire to the first and second electrodes to induce and maintaincardiac ventricular tachycardia. While the heart is in a state ofventricular tachycardia, a medical procedure can be performed.

In Example 2, the method of Example 1 can optionally be configured suchthat advancing the distal end portion of the bipolar pacing guidewireinto the left ventricle includes advancing a resiliently deformable,pre-formed curved shape into the left ventricle.

In Example 3, the method of Example 2 can optionally be configured suchthat the pre-formed curved shape includes a pigtail-shaped region thatturns through 540 degrees or more, and the first and second electrodesare spaced apart on the turns.

In Example 4, the method of any one or any combination of Examples 1-3can optionally be configured such that positioning the first and secondelectrodes includes positioning the first electrode a spaced distancefrom the ventricular wall and positioning the second electrode againstthe ventricular wall.

In Example 5, the method of Example 4 can optionally be configured suchthat the first electrode is an anode and the second electrode is acathode.

In Example 6, the method of any one or any combination of Examples 1-3can optionally be configured such that positioning the first and secondelectrodes includes positioning the first electrode against aventricular wall on a first side of a ventricular apex and positioningthe second electrode against a ventricular wall on a second side of theventricular apex.

In Example 7, the method of any one or any combination of Examples 1-6can optionally be configured such that transmitting electrical stimulithrough the guidewire to the first and second electrodes includestransmitting electrical stimuli through a first elongate conductorelectrically connected to the first electrode and transmitting electrodestimuli through a second elongate conductor electrically connected tothe second electrode.

In Example 8, the method of Example 7 can optionally be configured suchthat transmitting electrical stimuli through the first elongateconductor includes transmitting electrical stimuli through a corewireand a helical coil.

In Example 9, the method of any one of Examples 7 or 8 can optionally beconfigured such that transmitting electrical stimuli through the secondelongate conductor includes transmitting electrical stimuli through ahypotube or a braid and a helical coil.

In Example 10, the method of any one or any combination of Examples 1-9can optionally be configured such that transmitting electrical stimulito the first and second electrodes includes generating a current flow of4.0 mA or less between the electrodes.

In Example 11, the method of Example 10 can optionally be configuredsuch that transmitting electrical stimuli to the first and secondelectrodes includes generating a current flow of 3.0 mA or less betweenthe electrodes.

In Example 12, the method of any one or any combination of Examples 1-11can optionally be configured such that inducing and maintaining cardiacventricular tachycardia includes inducing ventricular rates of 120-220bpm and lowering the patient's blood pressure.

In Example 13, the method of any one or any combination of Examples 1-12can optionally be configured such that performing the medical procedureincludes delivering a balloon catheter over the pacing guidewire until adilatation balloon, at a distal end portion of the balloon catheter, ispositioned within a native aortic valve, and then radially expanding thedilatation balloon into contact with a native heart valve annulus.

In Example 14, the method of any one or any combination of Examples 1-12can optionally be configured such that performing the medical procedureincludes delivering a balloon catheter over the pacing guidewire until adilatation balloon, at a distal end portion of the balloon catheter, ispositioned within a native aortic valve, and then radially expanding thedilatation balloon to urge a prosthetic heart valve into contact withthe native aortic valve.

In Example 15, the method of any one or any combination of Examples 1-14can optionally be configured such that performing the medical procedureincludes delivering a balloon catheter over the pacing guidewire until adilatation balloon, at a distal end portion of the balloon catheter, ispositioned within a native mitral valve, and then radially expanding thedilatation balloon to urge a prosthetic heart valve into contact withthe native mitral valve.

In Example 16, the method of any one or any combination of Examples 14or 15 can optionally further comprise adjusting the electrical stimulitransmitted through the guidewire once the dilatation balloon isdeflated.

In Example 17, the method of any one or any combination of Examples 1-16can optionally further comprise sensing an electrophysiological responseto the electrical stimuli transmitted through the guidewire, andadjusting the transmitted electrical stimuli through the guidewire basedon the electrophysiological response.

In Example 18, the method of Example 17 can optionally be configuredsuch that sensing the electrophysiological response includes sensing ifless than a 1:1 capture of the left ventricle exists.

In Example 19, the method of Example 17 can optionally be configuredsuch that sensing the electrophysiological response includes sensing thepatient's systolic blood pressure or pulse pressure.

In Example 20, the method of Example 19 can optionally be configuredsuch that adjusting the transmitted electrical stimuli includesincreasing the electrical stimuli transmitted through the guidewire ifthe patient's systolic blood pressure is less than 70 mmHg or the pulsepressure is less than 20 mmHg.

In Example 21, the method of any one or any combination of Examples 1-20can optionally further comprise removably coupling a connector body to aproximal end portion of the bipolar pacing guidewire, includingelectrically coupling first and second terminals of the connector bodyto first and second elongate conductors respectively associated with thefirst and second electrodes.

In Example 22, the method of Example 21 can optionally be configuredsuch that removably coupling the connector body to the proximal endportion of the bipolar pacing guidewire includes preventing shortingbetween the first and second elongate conductors.

In Example 23, the method of any one or any combination of Examples 1-22can optionally be configured such that all elements or options recitedare available to use or select from.

The scope of the present methods should be determined with reference tothe appended claims, along with the full scope of equivalents to whichsuch claims are entitled. In the appended claims, the terms “including”and “in which” are used as the plain-English equivalents of therespective terms “comprising” and “wherein.” Also in the followingclaims, the terms “including” and “comprising” are open-ended; that is,a method that includes features or components in addition to thoselisted after such a term in a claim are still deemed to fall within thescope of that claim. Moreover, the terms “first,” “second,” “third,”etc. in the following claims are used merely as labels, and such termsnot intended to impose numerical requirements on their objects.

The Abstract is provided to allow the reader to quickly ascertain thenature of the technical disclosure. It is submitted with theunderstanding that it will not be used to interpret or limit the scopeor meaning of the claims.

What is claimed is:
 1. A method, comprising: advancing a distal endportion having a multi-planar shape of a bipolar pacing guidewire into aleft ventricle of a patient's heart, including positioning the distalend portion such that a first electrode and a second electrode locatedon the multi-planar shape are positioned against or spaced from a leftventricular wall of the heart; transmitting electrical stimuli throughthe guidewire to the first electrode and the second electrode to providebipolar pacing to the heart; and advancing a treatment device over theguidewire to the heart while maintaining the bipolar pacing providedthrough the first electrode and the second electrode.
 2. The method ofclaim 1, further comprising performing a medical procedure on the heartusing the treatment device while maintaining the bipolar pacing providedthrough the first electrode and the second electrode.
 3. The method ofclaim 2, wherein advancing the treatment device over the guidewireincludes delivering a balloon catheter over the guidewire until adilatation balloon, at a distal end portion of the balloon catheter, ispositioned within a native mitral valve.
 4. The method of claim 3,wherein performing the medical procedure includes radially expanding thedilatation balloon to urge a prosthetic heart valve into contact withthe native mitral valve.
 5. The method of claim 1, wherein advancing thedistal end portion having the multi-planar shape of the guidewire intothe left ventricle includes straightening and facilitating introductionof the multi-planar shape into a guide catheter using a loading tool. 6.The method of claim 1, wherein advancing the distal end portion havingthe multi-planar shape of the guidewire into the left ventricle includesdistributing advancement forces along a dispersed, radial path of themulti-planar shape.
 7. The method of claim 1, wherein positioning thedistal end portion of the guidewire in the left ventricle includespositioning a first plane of the multi-planar shape including the firstelectrode at an angle relative to second plane of the multi-planar shapeincluding the second electrode.
 8. The method of claim 1, whereinpositioning the distal end portion of the guidewire in the leftventricle includes positioning the first electrode, which serves as acathode, in direct contact with the left ventricular wall.
 9. The methodof claim 1, wherein positioning the distal end portion of the guidewirein the left ventricle includes positioning the first electrode againstthe left ventricular wall on a first side of a ventricular apex of theheart and positioning the second electrode against the left ventricularwall on a second side of the ventricular apex of the heart.
 10. Themethod of claim 1, wherein transmitting electrical stimuli through theguidewire to the first electrode and the second electrode includestransmitting electrical stimuli through a first elongate conductorelectrically connected to the first electrode and transmitting electrodestimuli through a second elongate conductor electrically connected tothe second electrode.
 11. The method of claim 1, wherein transmittingelectrical stimuli through the guidewire to the first electrode and thesecond electrode includes inducing and maintaining the heart in a stateof cardiac ventricular tachycardia.
 12. The method of claim 1, furthercomprising: sensing an electrophysiological response to the electricalstimuli transmitted through the guidewire; and adjusting the transmittedelectrical stimuli through the guidewire based on theelectrophysiological response.
 13. A pacing guidewire, comprising: anelongated body extending from a proximal end portion to a distal endportion and having an intermediate portion therebetween, the distal endportion having a multi-planar shape including a first electrode and asecond electrode positioned thereon, wherein the first electrode and thesecond electrode are configured to provide bipolar pacing to a heart ofa patient when the distal end portion of the elongate body is positionedin a left ventricle such that the first electrode and the secondelectrode are contacting or spaced from a left ventricular wall, andwherein the proximal end portion and the intermediate portion of theelongate body are configured to support delivery of an elongatetreatment device over the guidewire and to the heart while the distalend portion maintains bipolar pacing of the heart.
 14. The pacingguidewire of claim 13, wherein a first plane of the multi-planar shapeincluding the first electrode is disposed at an angle relative to asecond plane of the multi-planar shape including the second electrode.15. The pacing guidewire of claim 13, wherein the multi-planar shapecomprises a pigtail shape having a radius of curvature that is reducedtoward a distal end of the multi-planar shape.
 16. The pacing guidewireof claim 13, wherein the multi-planar shape comprises a dimension incross-section that is reduced toward a distal end of the multi-planarshape.
 17. The pacing guidewire of claim 13, wherein the multi-planarshape comprises a first loop nested within a second loop.
 18. The pacingguidewire of claim 13, wherein the first electrode and the secondelectrode are raised above an outer surface of the distal end portion ofthe elongate body.
 19. The pacing guidewire of claim 13, wherein theelongate body has an outer diameter ranging from 0.014 in to 0.038 in,inclusive.
 20. The pacing guidewire of claim 13, further comprisingthird and fourth electrodes positioned on the multi-planar shape. 21.The pacing guidewire of claim 13, further comprising a first elongateconductor extending from a proximal end portion to a distal end portionthat is electrically connected to the first electrode, and a secondelongate conductor, insulated from the first elongate conductor,extending from a proximal end portion to a distal end portion that iselectrically connected to the second electrode.